Human mesenchymal stem cells (hMSCs) have gained attention in tissue engineering applications because of their pluripotency. While it has been shown th at the addition of growth factors like TGF-3 promotes chondrogenesis [5] and -glycerophosphate promotes osteogenesis [117], biological modulation alone tends to produce tissue engineered constructs lacking the proper function characteristics for orthopaedic applications [34]. In addition to biologic mediators, differentiation of human mesenchymal stem cells (hMSCs) also depends upon the mechanical stimuli imparted by the extracellular matrix. This implies that in order to attain their mature biologic and mechanical characteristics, the hMSCs must receive sequentially appropriate cues from growth factors, cytokines, extracellular matrix, and mechanical factors. Cellular differentiation involves a highly coordinated cascade of biological mediators th at effect not only biological pathways but also the mechanical environment of the cell. As these cells differentiate and become increasingly specialized, they are likely to have altered mechanoplasticity.

Using a combination of mechanical engineering, biochemistry, and cellular and molecular biology techniques including oligonucleotide microarrays and confocal microscopy, the following studies set out to tackle three primary objectives:​ (1) to determine whether hMSCs have the fundamental ability to distinguish between dynamic tensile and dynamic compressive loading by regulating distinct gene expression patterns, and to determine whether these differences in gene expression could be related to specific features of mechanical stimulation:​ changes in cell shape and volume;​ (2) to determine whether dynamic tensile and compressive loading activate different mechanotransduction pathways than chondrogenic and osteogenic growth factors during early stage differentiation of human mesencyhmal stem cells;​ and (3) to determine how progressive chondrogenic differentiation of hMSCs affects their response to dynamic compression.

Knowledge of how hMSCs respond to different types of mechanical loading, how this response differs from a traditional growth factor approach of inducing cellular differentiation and how their responsiveness to mechanical stimulation varies with cell differentiation stage are all critical for the successful design of tissue engineering constructs th at are optimally organized for a specific mechanical function.